Cell-type, circuit and network mechanisms of adult oligodendrogenesis in memory storage and retrieval

项目摘要 少突胶质细胞前体细胞在整个过程中不断地在成人脑中产生髓鞘化的少突胶质细胞。 生活成人脑回路的活跃髓鞘形成已被证明对某些形式的学习很重要， 我们小组最近的工作表明，这是记忆储存和提取的关键过程。然而，在这方面， 虽然先前的工作已经为成人大脑中髓鞘可塑性的调节提供了重要的见解， 尚不清楚这一过程如何影响记忆回路中神经编码的动态性质。髓鞘形成 增加了单个轴突的传导速度，然而这如何转化为水平上的计算 对神经回路及其后续行为输出的了解甚少。因此， 存在于那些与成人轴突髓鞘形成相关的发现和那些描述神经系统髓鞘形成的发现之间。 编码动力学是记忆编码、巩固和回忆的基础。在这份提案中，我们的目标是 1）阐明小鼠内侧前额叶皮层中的细胞类型，这些细胞在一次注射后变成有髓鞘的。 学习经验，2）确定皮层回路的活跃髓鞘形成如何影响细胞代码， 支持记忆，3）活动依赖性髓鞘形成如何调节同步和区域间 内侧前额叶皮层、杏仁核和海马在恐惧记忆回忆中的联系 和4）在体内的少突胶质细胞前体增殖和分化的时间动态， 存储器编码这些研究将首次提供证据，证明新病毒与病毒之间的双向相互作用。 髓鞘形成和主动记忆编码合奏，并将阐明神经胶质细胞的基本机制， 学习和记忆过程中的信号。

PROJECT SUMMARY Oligodendrocyte precursor cells continually produce myelinating oligodendrocytes in the adult brain throughout life. Active myelination of adult brain circuits has been shown to be important for some forms of learning, and recent work from our groups has shown that this a crucial process in memory storage and retrieval. However, while previous work has provided essential insight into the regulation of myelin plasticity in the adult brain, it is not clear how this process impacts the dynamic nature of neural encoding within memory circuits. Myelination increases conduction velocity across individual axons, however how this translates to computations at the level of neural circuits and their subsequent behavioral outputs is poorly understood. Thus, a considerable gap exists between those findings related to axonal myelination in the adult and those that describe the neural coding dynamics that underlie memory encoding, consolidation and recall. In this proposal we aim to bridge this gap by 1) elucidating the cell types in the mouse medial prefrontal cortex that become myelinated after a learning experience, 2) determine how active myelination of cortical circuits impacts the cellular codes that support memory, 3) how activity-dependent myelination modulates the synchronization and interregional communication between the medial prefrontal cortex, amygdala and hippocampus during fear memory recall and 4) the temporal dynamics of oligodendrocyte precursor proliferation and differentiation in vivo after memory encoding. These studies will provide the first ever evidence for bidirectional interaction between new myelin formation and active memory encoding ensembles and will elucidate fundamental mechanisms of glial signaling during learning and memory.